Day 2 – Changes, challenges and complexities: ADHD across the life-course

Day 2 of Meeting of Minds 2017, held at the Hague, in the Netherlands, brought the audience two parallel plenary sessions which covered the challenges and complexities of diagnosing and treating children/adolescents and adults with ADHD and psychiatric comorbid disorders; key publications in ADHD from the past year; ADHD and the impact on families; management strategies across the life-course; and sustaining optimal managent of ADHD.

Plenary session

ADHD and co-occurring mental health conditions in adults

This exciting plenary session was moderated by Professor Martin Katzman (Stress, Trauma, Anxiety, Rehabilitation and Treatment [START] Clinic for Mood and Anxiety Disorders, Canada), who opened the session by highlighting what an interesting time it is in the world of adult ADHD and the important role the audience has in raising awareness of the condition.

The first presentation was by Professor Philip Asherson (Institute of Psychiatry Psychology and Neuroscience, King’s College London, UK) entitled ‘ADHD and co-occurring mental health conditions in adults’. He began by presenting the results from the US National Comorbidity Survey highlighting the high rate of mood disorders, anxiety (including post-traumatic stress disorder) and drug dependence in adults with ADHD.1 He then described the commonly associated features of ADHD that support differential diagnosis: emotional symptoms, developmental traits, education problems and cognitive deficits2 and the common symptoms seen in adults. He outlined the results from the MIRAD project, a study conducted in patients with ADHD with no comorbidities, which showed that pure ADHD is quite symptomatic (compared with patients without ADHD), thus demonstrating that symptoms including fatigue, concentration/forgetfulness, sleep disturbance, irritability and worry are not a result of comorbidities but ADHD itself.3 He noted that affective lability in this patient population was predictive of ADHD and results from anger rating scales showed that patients with ADHD were more angry more often than patients without ADHD.4 He went on to describe the symptoms and impairments of ADHD that can mimic other disorders such as anxiety, depression, personality disorder and bipolar disorder.5

He concluded his presentation by describing the treatment algorithm for adults with chronic mood instability which recommends that chronic trait-like mental health problems (inattention, hyperactivity, impulsivity, emotional dysregulation) should be initially assessed followed by screening for ADHD. The patient ought to then be classified into two categories: 1) those with no ADHD, where an alternative diagnosis should be established and treated accordingly; 2) those with ADHD, with or without psychiatric comorbid disorders. In those without a comorbidity or comorbid personality disorder, pharmacological treatment for ADHD ought to be initiated; in those with significant depression, bipolar disorder or another condition, the comorbid disorder should be treated first in most cases. He also noted that treatment strategies should be reviewed and additional treatments, for example, cognitive behavioural therapy or medication, be considered.6

The second presentation by Professor Roger McIntyre (University of Toronto, Toronto, Canada) entitled ‘Symptom overlap and differential diagnosis’ focused on the phenomenology of symptom overlap. He began by saying that there isn’t a zone of delineation between ADHD and other conditions and that it is important to keep in mind the convergence of cognition, which is central to the conditions of ADHD, bipolar disorder and other impulsive disorders. He described a conceptual framework for the overlap between ADHD and bipolar disorder, describing homotypic versus heterotypic continuity (ADHD early in life and bipolar disorder later in life), topography versus topology (convergence of neurobiology of ADHD and bipolar disorder and the abnormalities in structure and function of ADHD and bipolar disorder with discrete entities which overlap) and symptoms versus domains. He discussed the overlap between phenotypes and introduced the Research Domain Criteria (RDoC) which were developed, for research purposes, as new ways of classifying mental health disorders based on behavioural dimensions and neurobiological measures such as positive and negative valence systems, cognitive symptoms, systems for social processes and arousal/regulatory process7 highlighting that general cognitive functioning is central in bipolar disorder and ADHD. He talked about the dimensional approach to bipolar disorder, describing the manic, mixed and depressive categories of DSM-IV compared with the manic, manic with mixed features, depressive with mixed features, and depressive categories of DSM-5.2,8 He noted that the majority of patients with mood disorders sit in the middle with manic with mixed features and depressive with mixed features, and questioned whether it was these patients that had ADHD with mood disorder, or just ADHD, or whether these symptoms were secondary to ADHD. He went on to report the findings from key studies such as the International Disorders Collaborative project, which measured the mixed features encountered in adult patients with both major depressive disorder (MDD) and bipolar disorder9; the STEP-BD study10; and results from a study which examined anxiety and mixed states.11 He explained that the symptoms of ADHD overlap with binge eating, in areas such as reward functioning, distraction and impulsivity. He concluded his presentation by highlighting that research is increasingly under way, looking at the brain structure of adults with ADHD and mood disorders to examine the overlapping changes.

In the final presentation of this plenary session Dr Larry Klassen (Eden Health Care Services, Canada) presented on the topic of ‘Screening and diagnosis of ADHD in adults’. He began by describing the clinical markers which could be suggestive of adult ADHD such as childhood history and a family member diagnosed with ADHD, and the overlapping symptoms of ADHD and comorbidities. He posed the question “Who do you screen?”, and recommended screening all patients with MDD, anxiety and bipolar disorder; those with substance-use disorders (especially those who are receiving methadone); patients with a family history or child with ADHD; adults who are not reaching their full potential; adults with motor vehicle issues; and adults exhibiting symptoms of forgetfulness. He provided the audience with an extremely useful pneumonic for screening for adult ADHD “PDF”: Procrastination, Distractibility, Forgetfulness (Courtesy of Timothy Bilkey). With regard to the screening tools he uses in clinical practice, Dr Klassen described the ADHD Self-Report Scale (ASRS v1.1); Wender-Utah Rating Scale; Barkley Screener; Conners Adult ADHD Rating Scales (CAARS) and noted that there will shortly be a new ASRS v1.2 available. He concluded the presentation by describing two validated diagnostic interviews available to help with diagnosis: the DIVA 2.0 and ACE+.

Professor Roger McIntyre, Professor Philip Asherson and Dr Klassen were then joined by Professor Guy Goodwin and Professor Toni Ramos on stage for a stimulating expert panel discussion moderated by Professor Katzman. Questions from the audience covered topics such as whether there was a risk of mania in patients with ADHD and bipolar disorder treated with psychostimulants; cognitive trajectories in autism spectrum disorders, bipolar disorder and ADHD; ASRS v1.1 versus ASRS v1.2; and the interface between borderline personality disorder and bipolar disorder in ADHD phenotypes.

Professor Katzman: “Be an advocate – we are in a unique position to share and work together to enhance outcomes for those adults that are misdiagnosed.”

Dr Greg Mattingly and the panel

Plenary session

Challenges and complexities of ADHD and co-occurring mental health conditions in children and adolescents

The first speaker at this parallel plenary session was Professor Luis Rohde (Federal University of Rio Grande do Sul, Brazil), who introduced the topic with his short opening presentation entitled ‘Challenges and complexities of ADHD and co-occurring mental health conditions in children and adolescents: Setting the scene’. He highlighted the importance that seminal publications have attached to comorbidity in ADHD. The most commonly reported comorbidities across three international studies were oppositional defiant disorder, anxiety, conduct disorder and depression;12 however, clinical comorbidities, such as type I diabetes and obesity, may also be an issue. Professor Rohde then presented data from three studies that all suggested that ADHD comorbidities may carry the outcome risk for substance use, neuropsychological impairment and traffic accidents. Finally, the audience were reminded that comorbidities should be a consideration when deciding upon a first intervention in the clinic.

In the second talk of the session, ‘ADHD: A highly comorbid condition’, Professor Tobias Banaschewski (Central Institute of Mental Health, Mannheim, Germany) provided an overview of the global prevalence of ADHD, then showed how there has been little change in prevalence estimates over the past 25 years.13 However, at a more local level, prevalence rates can be quite variable, even within countries.14 ADHD comorbidities, however, are reported to occur at similar frequencies between countries and affect individuals at predictable stages of childhood/adolescence.

Professor Banaschewski emphasised that ADHD comorbidities increase in frequency throughout the lifespan and contribute significantly to functional impairment. He highlighted data from two independent longitudinal case-controlled studies that showed an increased lifetime risk of comorbid mood, anxiety, antisocial and addictive disorders compared with controls. A recent meta-analysis also indicated that children with ADHD were 40% more likely to be obese than children without ADHD.15

In summing up, it was shown that ADHD comorbidities can hinder diagnosis, impact on health-related quality of life and on patient mortality.

The next presentation, ‘Managing the more challenging and complex cases’, by Dr Greg Mattingly (Washington University in St Louis, MO, USA) provided an overview of treatment options for children with ADHD and other comorbid conditions. A key theme of the presentation was the optimisation of initial treatments, based on the correct identification of comorbidities at diagnosis. Dr Mattingly emphasised that the presentation of mental health conditions frequently change as the brain matures; in the case of ADHD, cortical maturation is delayed compared with controls, particularly in prefontal regions.

The question of whether mood disorders or ADHD should be treated first was also discussed, with some evidence suggesting that early treatment of ADHD can reduce rates of antidepressant resistance.16 The importance of separating the symptoms of pre-pubertal bipolar disorder from those of ADHD was also reviewed. The best differentiating factors, predictive of bipolar disorder over ADHD, were elevated mood, grandiosity, racing thoughts, decreased need for sleep and hypersexuality.17 Results from an 8-year follow‑up study of medication use in pre-adolescent onset bipolar disorder showed that 62.6% received any antimanic medication at any time, 77.4% received medication for ADHD and 64.3% received antidepressants.18 Another study showed that ADHD medication does not affect treatment for bipolar disorder.19

Dr Mattingly went on to show, using pooled data from crossover studies, that responses to ADHD medication vary, and that 13% of children were unresponsive to methylphenidate and amphetamine treatments.20 He highlighted the potential advantages of combination therapy in children who were non-responsive to stimulants and in complex cases.21

Breaking headlines in ADHD: 2016/17

Review of key publications

This session gave the audience a unique and valuable opportunity to find out which publications from the previous year were considered most impactful by the expert panel members. Key publications were identified and discussed by Professor Tobias Banaschewski, Professor Luis Rohde, Professor David Coghill, Professor Marina Danckaerts, Professor Paulo Mattos and Professor Martin Katzman. The key conclusions from the publications are outlined below.

Results from this study show an increased risk of motor vehicle crash risk in adolescents with ADHD, compared with non-ADHD controls. This effect was independent of age, sex, and driving experience. Medication had no effect on crash risk.

This large study followed a US national cohort of over 2 million patients with ADHD over a 10-year period. Inter-individual analyses of motor vehicle crash rate were compared between medicated and non-medicated months using insurance claims data. The rate of crashes was reduced by 38% by medication use, suggesting that around 20% of motor vehicle crashes in adults with ADHD may have been avoided if medication was continued throughout the study period.

This population-based cohort study assessed educational outcomes in 766,244 children attending Scottish schools between 2009 and 2013. Children receiving medication for the treatment of ADHD were compared with children without ADHD, and were found to have poorer outcome measures. These data highlight that even with medication, children with ADHD may be impaired at school.

Data from Swedish national registers was used to explore the effect of ADHD medication on higher education performance in 930 patients with ADHD. Test scores from periods when patients were taking medication were compared with scores from periods of non-medication. ADHD medication use was associated with significantly higher test scores, although the clinical relevance of the effect size is unclear.

This paper presents results from the 16-year follow-up of young adults from the Multimodal Treatment Study of Children with ADHD (MTA).27 Key findings included a dose-dependent suppression of growth, and no significant effect on symptoms compared with a local population control group. One limitation of this study was that medication use was only monitored for 10 years, while symptom control was assessed at 12, 14 and 16 years. It is therefore difficult to know if medication was continued at these time points.

This Danish historical perspective study examined when in their lifetime patients with ADHD are most likely to become parents. Compared with individuals without ADHD, patients with ADHD were significantly more likely to have children at 12-16 years, and at 17-19 years. Targeted sexual education and contraceptive counselling may be appropriate in these groups.

The aim of this meta-analysis was to assess the risk of developing substance-use disorders in patients with ADHD and other mental health problems. A total of 37 studies were assessed and indicated that patients with ADHD have increased risk for alcohol, tobacco and drug addiction. Similar results were found for patients with oppositional defiant disorder, conflict disorder and depression.

The relative risk of suicide attempt in patients receiving treatment with methylphenidate was compared with periods of non-treatment in this population-based, self-controlled study. A total of 25,629 patients were assessed over the 5-year study period. Incidence of suicide attempt was higher in the period immediately before onset of methylphenidate treatment. No causal relationship between methylphenidate treatment and suicide attempt was found.

Professor Katzman: “Comorbidity is important in defining the trajectory to suicide.”

Professor Coghill

Plenary session

ADHD: a family affair

Professor Marina Danckaerts (University of Leuven, Belgium) got the final plenary sessions under way with her presentation entitled ‘ADHD: a family affair’. The interactions between a child’s ADHD symptoms, their parents’ behaviours and the family unit were explored, and the potential impact on treatments assessed.

Results from large studies of twins in Sweden have revealed an increased risk of ADHD in siblings, but not cousins of individuals with ADHD.32 Similarly, meta-analysis of twin studies have estimated the heritability of clinically diagnosed ADHD to be 88% overall, and 72% in adults.33 These studies confirm a strong genetic component in the heritability of ADHD, but also show that other factors must also play a role.

Professor Danckaerts went on to present results from a meta-analysis of twin and adoption studies (n=490) which examined internalising and externalising psychopathology prior to adulthood, where results showed that shared environment accounted for 10-19% of the variance within conduct disorder, oppositional defiant disorder, anxiety, depression; however, ADHD appeared to be largely genetic origin.34 She then discussed the results from a population study in Sweden which estimated the heritability of ADHD as 89% with non-shared environment accounting for 11% of the variance.32

The role of evocative correlation in predicting future ADHD was highlighted. This is when the child elicits parental reactions that further increase the risk of ADHD.35 It was also shown that genetic influences of ADHD are highest in low-risk environments (when parental involvement is high).36

The problems affecting families with a child with ADHD were examined; these were shown to have significant impact on measures of quality of life. It was also demonstrated that short-term ADHD prognosis can be influenced by the family, with high levels of warmth and involvement correlating with attenuation of symptoms, and the development of comorbid symptoms associated with parental aggression, maternal depression or inconsistent parenting.37

In conclusion, Professor Danckaerts advocated early intervention and treatment of both children and parents with symptoms of ADHD. Parenting interventions for adults with ADHD may also provide benefits to the family unit, but should be tailored to the individual’s needs and abilities.

Greg Mattingly returned to the stage to deliver an informative talk on ‘The clinical challenges of genetics, neurology and environmental context’. During the presentation, he addressed areas in which clinical outcomes may be improved by changes in clinical practice, covering diagnosis, transition management and optimisation of medication.

The complex aetiology of ADHD means that symptoms often differ between patients, and there are several areas of impairment that could potentially be addressed.

Treatment persistence was identified as a key concern, particularly in adolescents. Results from several studies have shown a drop-off in ADHD medication adherence over this period.38-40

From his own clinical experience, Dr Mattingly identified the following factors as important in improving compliance and persistence to ADHD treatments:

active case management

psychoeducation

once-daily education

shared decision-making

rapport with the treatment provider.

Results were presented from a linguistic study that assessed physician-patient interview transcripts for qualitative and quantitative aspects that correlated with patient satisfaction. It was found that overall visit length had little correlation with patient satisfaction.41 Several gaps in treatment were identified, including inadequate use of ADHD rating scales, and use of inconsistent assessment questions. Examples of identified problems that negatively impacted on the patient’s experience included:41

focusing too heavily on school and deficits

failure to stress the importance of adherence and persistence

exclusion of children from the discussion.

Dr Mattingly concluded his talk by discussing the importance of optimising symptom reduction across the lifespan by adjusting treatments in response to changes in ADHD presentation.

The final speaker was Professor David Coghill (University of Melbourne, Australia) who gave an inspiring overview of the successful Dundee ADHD Clinical Care Pathway (DACCP) project entitled ‘Sustaining optimal management of ADHD’.

ADHD can be relatively easy to treat; however, achieving sustained benefit in patients with ADHD can be difficult. Although most parents report satisfaction with their child’s ADHD treatment, many still experience considerable behavioural challenges across the day.42

The aim of the DACCP project was to emulate the sustained, long-term improvements in ADHD symptoms seen in the MTA study.43,44 An important outcome from the MTA studies was that the standard of care must be maintained over time for treatment benefits to be sustained.

Two key elements of the DACCP design were:

the inclusion of an intensive 4-week dose titration protocol, focused on symptom reduction and optimisation of treatment

Professor Coghill discussed some results from DACCP, where mean SNAP/ADHD-RS-IV score decreased from 2.5 at baseline, to 0.7 at the end of titration, and to 0.8 at the most recent visit. The mean duration of treatment was 43 months (range 1-119 months), and the mean dose of methylphenidate was 52 mg/day.45 Rates of remission in DACCP were 44% pre-change and 67% post-change.

Potential modifications to the DACCP approach that would allow its application to adult populations were suggested. These included using expanded DSM-5 prompts when rating symptoms, and adopting different approaches to the management of comorbidities.

Deault LC. A systematic review of parenting in relation to the development of comorbidities and functional impairments in children with attention-deficit/hyperactivity disorder (ADHD). Child Psychiatry Hum Dev 2010; 41: 168-192.

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